Xu Xian, Zhu Guo-Qin, Zhang Kai, Zhou Yi-Chan, Li Xiao-Lin, Xu Wei, Zhang Hao, Shao Yun, Zhang Zhen-Yu, Sun Wei-Hao
Department of Geriatric Gastroenterology, The First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, China.
Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Oncotarget. 2017 Oct 6;8(54):92770-92777. doi: 10.18632/oncotarget.21576. eCollection 2017 Nov 3.
Ursolic acid (UA) induces apoptosis in gastric cancer cells by inhibiting cyclooxygenase-2 (COX-2). Paclitaxel (PTX) is an important chemotherapy agent used to treat solid tumors. We evaluated the antitumor activity of UA in combination with PTX against gastric cancer cells and investigated the mechanisms underlying the combined effects. A cytotoxicity test and flow cytometry were utilized to study the effects of UA and PTX on proliferation and apoptosis, respectively. To further elucidate the mechanism, Western blot analysis was used to assess changes in the expression of a series of related proteins, including COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, and Bax. UA and PTX dose- and time-dependently inhibited BGC-823 and SGC-7901 gastric cancer cell proliferation. Combined delivery of UA and PTX synergistically reduced cell proliferation and induced apoptosis in these cells by lowering COX-2, PCNA, and Bcl-2 expression and by increasing Bax expression. These results indicate that the synergistic inhibition of proliferation and induction of apoptosis by UA and PTX may be induced by reducing COX-2 expression in gastric cancer cells.
熊果酸（UA）通过抑制环氧化酶-2（COX-2）诱导胃癌细胞凋亡。紫杉醇（PTX）是一种用于治疗实体瘤的重要化疗药物。我们评估了UA与PTX联合对胃癌细胞的抗肿瘤活性，并研究了联合作用的潜在机制。分别利用细胞毒性试验和流式细胞术研究UA和PTX对增殖和凋亡的影响。为进一步阐明机制，采用蛋白质印迹分析评估一系列相关蛋白表达的变化，包括COX-2、增殖细胞核抗原（PCNA）、Bcl-2和Bax。UA和PTX剂量和时间依赖性地抑制BGC-823和SGC-7901胃癌细胞增殖。UA和PTX联合给药通过降低COX-2、PCNA和Bcl-2表达以及增加Bax表达，协同降低这些细胞的增殖并诱导凋亡。这些结果表明，UA和PTX对增殖的协同抑制和凋亡诱导可能是通过降低胃癌细胞中COX-2表达来实现的。
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